Activation of the cardiac ATP-sensitive K+ channel by ER-001533, a newly synthesized vasorelaxant

W. K. Shen, R. T. Tung, Y. Kurachi

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Effects of ER-001533 (ER), a newly synthesized vasorelaxant, on the membrane currents were examined in single ventricular cells of guinea pigs. The patch-clamp technique was used in the 'whole-cell' and 'inside-out' patch configurations. In the whole-cell clamp condition, ER induced a time- independent K+-dominant current, which was inhibited by glibenclamide (1-3 μM), suggesting that ER activated the cardiac ATP-sensitive K+ channel (K(ATP)). To elucidate the mechanism of ER-mediated K(ATP) channel activation, the drug was applied to the inside-out patches before and after channel 'run-down.' Since nucleotide diphosphates could induce the channel openings after complete run-down, effects of the drug on the nucleotide diphosphate-induced channel openings were also examined. Before run-down, ER activated the K(ATP) channel only in the presence of ATP. ER shifted the relation between [ATP](i) and the channel activity to the right in a concentration-dependent fashion without a significant alteration of the slope. After channel run-down, ER did not affect the channel openings either in the absence or in the presence of UDP. However, ER could relieve the ATP- γ-S inhibition of the UDP-induced channel openings. Thus, we conclude that ER antagonizes the inhibitory effect of ATP on the K(ATP) channel in a competitive manner, thereby enhancing the channel openings.

Original languageEnglish (US)
Pages (from-to)1054-1061
Number of pages8
JournalCirculation research
Volume70
Issue number5
StatePublished - May 4 1992

Keywords

  • ATP-sensitive K channel
  • ER-001533
  • cardiac myocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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